Epithelial cells derived from the livers of 10-day-old Fischer 344 rats are used as a model system for studying the mechanism of carcinogenesis resulting from an insufficiency of methyl donors. Liver cells transformed by ethionine, a hepatocarcinogenic methionine antagonist, and the corresponding control cells have been examined histochemically, immunochemically and morphologically. The data obtained provide evidence for the epithelial nature of the cells and their derivation from liver epithelium, as well as indicate cellular alterations which accompany transformation. Transformation of liver cells, as manifested by growth in soft agar, has also been achieved following treatment with 3-deazaadenosine (DAA). This compound is metabolized to 3-deazaadenosylhomocysteine, a potent inhibitor of S-adenosylhomocysteine (AdoHcy) hydrolase, and results in an accumulation of AdoHcy, a competitive inhibitor of most physiological methylation reactions.